SPECIFIC AIM: To determine the role(s) of eosinophil effector functions in pulmonary remodeling and lung dysfunction using an established model chronic allergen provocation in conjunction with transgenic and gene knockout mice devoid of eosinophils and specific granule proteins, respectively. STUDY DESIGN: A line of mice uniquely>devoid of eosinophils was created as a solution to the logistical problem of defining the importance of eosinophil activities in allergic respiratory inflammation. This proposal utilizes these novel eosinophil-less mice as well as knockout mice deficient of the abundant secondary granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1). The Aims of the proposal will initially be to determine the role(s) of eosinophils in remodeling events and sustained lung dysfunction following chronic allergen provocation by comparing allergen-induced pathologies in wild type vs. eosinophil- less mice. Subsequent mechanistic studies will define the contribution of degranulation and the effects mediated by the release of the abundant secondary granule proteins using granule protein knockout mice. RELEVANCE: Studies abound that either support or provide evidence against the hypothesis that eosinophil activities mediate remodeling and sustained lung dysfunction. Conceptual jumps defining eosinophil activities has had to await the development of mice deficient of these leukocytes and knockout mice deficient of specific effector functions. The development of these lines of mice now provides the fulcrum which will allow me to determine the role(s) of eosinophil effector functions in the lung following allergen provocation. [unreadable] [unreadable]